Project Summary/Abstract In this grant application, framergy, in collaboration with Baylor College of Medicine, will demonstrate a promising next- generation skin cancer prevention technology, with the ultimate goal being successful commercialization and life-changing public benefit. The team will utilize a novel class of nanostructured material, called Metal-organic Frameworks (MOFs), to prevent ultraviolet (UV)-induced melanoma and squamous cell carcinomas by blocking UV light and absorbing cancer triggering, byproduct free-radicals on the skin. Studies have shown that exposure to solar radiation (UV/Visible radiation) from the sun results in sunburn and has been linked to premature skin aging, immunosuppression and skin cancer. The number of new cases of melanoma has been increasing for at least 30 years. Sunscreen may help decrease the amount of UV radiation to the skin. According to National Cancer Institute, wearing sunscreen can help prevent actinic keratoses, scaly patches of skin that sometimes- become squamous cell carcinoma. Despite increased use of sunscreens over the years, skin cancer rates have continued to rise. There are two impediments to the development of next generation sunscreens: 1) The insufficient magnitude of UV protection of current products on the market, including strong inorganic UV protectors like TiO2 and ZnO, and 2) the fact that these inorganic protectors generate reactive oxygen species (ROS) which combine with organic compounds in the formula, or on the skin, to form harmful byproducts. Recent advances in porous coordination network materials, such as MOFs, can address the need for improved breadth and magnitude of UV protection while capturing the toxic reactive oxygen species and radical byproducts generated under solar radiation. During Phase I, framergy will down-select the optimal titanium MOF for the composition through UV absorbance testing, heat of adsorption testing, water stability testing and controlled particle size synthesis. Further, framergy will take a top down and bottom up approach to demonstrate the performance of organic peroxide scavenging of the MOF. Baylor College of Medicine will assist this technology development activity by performing biological experiments in 2D cell models measuring the effects of UV irradiation on DNA damage and ROS production, with and without the application of MOFs. These assays will be imaging-based, medium and high throughput automated experiments coupled with single cell analytics. This will help shed light on the role of MOFs in the prevention of UV induced melanomas. Testing MOFs in 3D skin models across Phase I and II will further strengthen results ahead of preclinical studies. In the Phase II period, framergy and the BCM team will collaborate with Texas Institute for Preclinical Studies (Texas A&M University) to conduct preclinical trials to conduct cytotoxicity and photogenotoxicity studies to transition the product development activities from cell-level to large animal preclinical trials.